The current study, part of a larger study investigating the development of a phytoestrogenic nutraceutical from Cyclopia, focuses on activity-guided fractionation of SM6Met from C. subternata to identify the compound(s) responsible for its desirable estrogenic attributes, namely ERβ agonism, ERα antagonism and antagonism of E2-induced breast cancer cell proliferation [30–32]. This evidence concerns the gene ESR1 and breast carcinoma.